Derivatives of 2-aminoindanes

ABSTRACT

This invention relates to new derivatives of 2-aminoindane, namely N-phenyl (or 2-pyridyl)-N-di-R1,R2-aminoalkyl (or aminoalkanoyl)-2-aminoindanes wherein R1 is hydrogen or a lower alkyl, hydroxyalkyl, alkenyl or alkynyl radical, R2 is a lower alkyl, hydroxyalkyl, alkenyl or alkynyl radical, whereby R1 and R2 may form together with the attached nitrogen atom a nitrogenous heterocyclic ring, as well as the acid addition salts of said derivatives. The new compounds are valuable therapeutic agents for the treatment of heart arrhythmy.

United States Patent Vanhoof et al.

Dec. 2, 1975 DERIVATIVES OF Z-AMINOINDANES Inventors: Pierre M. Vanhoof;Pierre M.

Clarebout, both of Brussels,

Belgium Assignee: A. Christiaens Societe Anonyme,

Brussels, Belgium Filed: Mar. 8, 1973 Appl. No.2 339,454

Related US. Application Data Continuation-impart of Ser. No. 99,643,Dec. 12, 1970, abandoned.

Foreign Application Priority Data Dec. 19, 1969 United Kingdom 6200/69US. Cl ..260/293.62; 260/247.2 A; 260/247.5 B; 260/268 BC; 260/295 F;260/295 K; 260/296 B; 260/326.33; 260/326.85; 260/561 A; 260/570.5 P;424/248; 424/250; 424/267; 424/274; 424/320; 424/330 Int. CI. C07D295/14 Field of Search 260/247.2 A, 247.5 B, -268 BC, 260/293.62, 295 F,295 K, 296 B, 326.33, 326.85, 561 A, 570.5 P

[56] References Cited UNITED STATES PATENTS 2,505,133 4/l950 Miescher ctal. 260/309.6 2,670,371 2/1954 Cusic 260/570.5 2,670,376 2/1954 Scudi etal.... 260/570.5 2,687,414 8/1954 Cusic 260/570.5

FOREIGN PATENTS OR APPLICATIONS 106,506 2/1963 Czechoslovakia 260/570.5PA

Primary Examiner-G. Thomas Todd Attorney, Agent, or Firm-Sughrue,Rothwell, Mion, Zinn & Macpeak [57] ABSTRACT The new compounds arevaluable therapeutic agents for the treatment of heart arrhythmy.

12 Claims, N0 Drawings DERIVATIVES OF Z-AMINOINDANES REFERENCE TOCROSS-RELATED APPLICATIONS This application is a continuation-in-partapplication of our earlier co-pending application, Ser. No. 99,643,filed on Dec. 12, 1970, now abandoned and claims priority from Dec. 19.1969 based on British Provisional Patent Application 62073/69; Nov. 26,1970 based on the Complete Specification of British Provisional Pat.Application 62073/69; Feb. 5, 1973 based on British Provisional Pat.Application 5631/73; Mar. 1, 1973' based on British Provisional Pat.Application 9988/73; Mar. 1, 1973 based on British Provisional Pat.Application 9987/73; Mar. 2, 1973 based on British Provisional Pat;Application 10302/73; Mar. 2, 1973 based on British Provisional Pat.Application 10303/73; Mar. 2, 1973 based on British Provisional Pat.Application 10305/73; and Mar. 2, 1973 based on British Provisional Pat.Application 10304/73, respectively.

SUMMARY OF THE INVENTION This invention relates to new nitrogenousorganic compounds and to pharmaceutical compositions containing saidcompound as active ingredients.

The new nitrogenous organic compounds according to this invention arederivatives of 2-aminoindane of the general formula:

wherein n is equal to 1,2 or 3, Z represents two hydrogen atoms or anoxygen atom, the (CI-l group having a straight or branched claim, Rrepresents hydrogen, a lower alkyl or hydroxylakyl radical containing 1to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or3 carbon atoms, R represents a lower alkyl or hydroxyalkyl radicalcontaining 1 to 3 carbon atoms or a lower alkenyl or alkynyl radicalcontaining 2 or 3 carbon atoms, whereby R and R may be identical ordifferent and may also form together with the adjacent nitrogen atom anitrogenous heterocyclic ring, A is a 2-pyridyl radical, anunsubstituted phenyl radical or a phenyl radical substituted by at leastonesubstituent in the ortho, meta and/or para position, and B representshydrogen, an alkoxy r'adical containing 1 to 3 carbon atoms or a groupof the formula in which R, and R, which may be identical or differentrepresent a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbonatoms, whereby R may also represent hydrogen, whereas R and R may alsoform with the attached nitrogen atom a nitrogenous heterocyclic ring, aswell as the acid addition salts of said derivatives of formula (I).

This invention relates also to pharmaceutical compositions namely forthe treatment of heart arrhythmy containing at least one compound of thegeneral formula (I), together with a pharmaceutically acceptableexcipient or carrier.

- DETAILED DESCRIPTION OF THE INVENTION It has surprisingly been foundthat the compounds of the general formula I are very active for thetreatment of heart arrhythmia.

Said compounds can be used for the treatment of various heart diseasessuch as premature heart contractions, ventricular and surpraventriculartachycardias either idiopathic or subsequent to cardiopathia or tocoronary disease, cardiac arrhythmias due to digitalin intoxication, aswell as atrial fibrillation and flutter, particularly in the earlystage.

It is known (see Koch-Weser, J. Arch. Int. Med. 129; 763, 1972) thatnone of the presently available antiarrhythmic agents are satisfactoryfor the prophylaxis of tachycardias and filbrillation of ventricularorigin.

The oral activity of the known antiarrhythmic agents, such asprocainamide or lidocaine, is either too short leading to multiple dayand night administration (for example with procainamide) or too low tobe of some practical utility (for example with lidocaine) or theirtherapeutic activity is conjugated with frequent and dangerous sideeffects, such as hypotension (with procainamide), sudden death,agranulocytosis or idiosynerasy.

The compounds of general formula I according to this invention are veryactive when orally administered, although they may also be administeredparenterally. They have also a long activity duration and are notdepressant for the myocardial function.

Applicants do not know any orally active antiarrhyth-- mic agent whichdoes not act at the same time as a depressant of the myocardialfunction.

The oral antiarrhythmic activity of the compounds of formula I has beenproved by tests on rats using aconitine which is a compound causingpremature heart contractions and death of the animals.

The method used for these tests is described hereafter:

Animals:

Male or female rats with a body-weight ranging from 380 to 450 g.

Aconitine solution:

312 ug aconitine nitrate/1 ml physiological saline.

Solution of the compound to be tested:

0.75 in distilled water.

Method:

Six random selected animals are required for each compound to be tested.The compound is administered by oral route at the dose of mg/kg (lml ofthe 0.75 solution/ g of body-weight) 75 minutes before the intravenousperfusion of the aconitine solution is initiated.

Control groups of animals are treated only with distilled water (Iml/lOO g).

Sixty minutes after the administration of the compound to be tested, theanimals are anesthesized by an intraperitoneal injection ofPentobarbital (50 mg/kg) and the jugular vein is dissected. 'A catheteris introduced in the vein and fixed by a ligature The ECG (D IIderivation) is then continuously recorded. The perfusion of theaconitine solution is started 75 minutes after the administration of thecompound to be tested. The volume delivered by the injection devicebeing 0.287 ml/minute, the dose of aconitine nitrate administered is0.895 ug/minute (0.20 0.24 [Lg/100 g/min. according to the minimal andmaximal weight of the animals). The experience is stopped as soon as thefirst extrasysof the antiarrhythmic activity by oral route of a greatnumber of acid addition salts of compounds of formula I, compared to theactivity of two well known antiarrhythmic agents (procainamide andlidoeaine): toles are appearing and the time elapsed from the beginningof the perfusion is noted.

The results are expressed as the mean total dose of aconitine injectedin a group of animals.

The relative activity between a tested compound and 5 a referencesubstance (lidocaine, procainamide) is computed in the following way:

. Zi .tm F 100 where R Mean dose of aconitine injected in the animalstreated by the reference substances.

The following table gives the results of the evaluation TABLE 1Compounds of formula I 7: activity versus type of Lido- Proeaina- A B nZ R R. salt caine mide phenyl H 2 H. H C- .H mono- 683 871 hydrochloridephcnyl H 2 H- CH CH mono- 299 382 hyd rochloride phcnyl H 2 H- CnH7 Hdihydro- 400 510 chloride phcnyl H 3 H- C- H H mono- 653 833hydrochloride 2-py- H 2 H C H H mono- I283 I644 ridyl hyd rochloridephcnyl H 2 H CH CH mono- 404 516 a CH CH hydro- CH? Ch chloride phenyl H1 H CH CH mono- I89 242 hydrochloride phcnyl H 1 H C H C H mono- 261 332hydro- V chloride phc- H l H: morpholino mono- 77 99 nyl hydrochloridephe- H 2 H methylpipcramono 285 365 nyl zino hyd ro chloride phc- H 2 HCH C l-l monol04l 1330 nyl hydrochloride phe- H 2 H C- H H mono nylhydrochloride phc- H 2 H H CH CH mono- 322 4H n \'l OH hydrochloridephe- H 3 H- piperidino mono- 505 645 nyl hydrochloride 26 H 2 H. H, C-.H,, mono 118 I52 chlohydrorophechloride nyl 2- H 2 H C. .H C- H,fumarate 402 513 chlorophcn \'l 3' H 3 H. H, C H, oxalate 32-1 414chlorophcnyl 4- H 2 H C H, C H, fumaratc 179 228 chlo- TABLE l-continuedCompounds of formula l /1 activity versus type of Lido- Procaina- A B n7. R R salt cainc midc te phcnyl OCH 2 H H C .H fumaratc 98l l25l C- -H,phcnyl 2 H: CH CH3 dihyrlro- 247 3l6 C- -H,-, chloride C. .H phcnyl N 2H- .H (:H; dihydro- 416 53! u a chloride OH, phony] N 2 H CH CH, difuma-238 303 CH1 rate phenyl H l C. H C- .H monohy- 367 468 drochloridephcnyl H l CH CH monohy 158 202 drochloride H 2 0 CH;, CH monohy- 531677 phcnyl drochloridc phenyl H 2 O (:H,-, C. .H,-, monohy- 1034 I319drochloride phcnyl OCH; l H C. -H monohy- 558 713* drochloride phenyl H2 H C. .H,, monohy- 733 936 drochloride phcnyl H l O methylpimonohy- 332423 perazino drochloride phcnyl H 2 piperimonohy- 656 837 dinodrochloride phenyl H 2 O methylpimonohy- 544 694 perazino drochloridephcnyl OCH 2 O piperimonohy- I578 2013 dino drochloride phenyl OCH; l Opiperimonohy- 284 363* dino drochloridc phenyl H 1 H pipcrimonohy- 402538 dino drochloridc 2-py- H 2 H. CH CH monohy- I276 I628 ridyldrochloride 2-p H l H. C. H C H 5 oxalate I078 I376 ridyl 2-py- H 1 Hpiperimonohy- 784 I000 ridyl dino drochloride 2-p H 2 H. H C Hmonohyl320 1780 ridyl drochloride *The Compounds in question have beenadministered at a doseof 37.5 mg/kg,

The anti-arrhythmic activity of the compounds of formule I has beenconfirmed by various other tests, namely the extrasystolic arrhythmiainduced in the dog by administration of a subtoxic dose of ouabain, theexperimental myocardic infraction in the dog and the electricallyinduced ventricular fibrillation in the dog.

Clinical investigations have confirmed the potent antiarrhythmic effectsof the compounds of formula (1). Up to now, more than 600 patients havebeen successfully treated with various compounds according to thisinvention.

The compounds of the formula I may be administered orally orparenterally.

Oral preparations may be administered under the form of capsules,tablets, pills and the like. Each capsule, tablet or pill may containfrom to 200 mg of a compound of formula I as active ingredient, togetherwith pharmaceutically acceptable excipients or carriers.

Parenteral preparations may consist in a solution for perfusion or forintravenous or intramuscular injection. Such a solution may contain from0.2 per thousand to 2 per thousand of a compound of formula I.

The parenteral preparation may be either a solution which may bedirectly used for the perfusion and contains a propoprtion of the activeingredient within the above limits, or a concentrated solutioncontaining 1 to 10% of the active ingredient, said concentrated solutionbeing diluted when administered to the patient.

The initial dose of active ingredient may be of 200 to 800 mg per dayduring 2 or 3 days, the maintenance dose being of about mg to 300 mg perday.

If a single dose is sufficient for obtaining the therapeutic effect,this dose is generally comprised between and 300 mg.

The active ingredient may be administered at the same time by theparenteral route (for example by perfusion) and by the oral route.

The compounds of the general formula (I) may be prepared by variousprocesses.

First process.

c1 (CH-1),, COCl This process involves the reaction of a N-phenyl [or 5in which Z O SO as to Obtain an acylated com-N-(2-pyridyl1-2-aminoindane of the formula in which A and B have theabove meanings with sodium amide (NaNH and with a halogenated amine ofthe formula in which Hal represents a halogen atom, preferably achlorine atom, whereas n, R, and R have the above meanings.

Second process This process involves the acylation of compound offormula (II) with an acid, chloride of the formula:

the subsequent reduction of the acylated compound of formula (V) bymeans of aluminum lithium hydride into a compound of the followingformula:

in which n has the above meanings, the obtained compound of formula (VI)being finally alkylated by means of a primary or secondary amine of theformula:

(Vll) Third process:

This process involves the acylation of a compound of formula (ll) withan acid chloride of the formula:

pound of the formula:

the subsequent N-alkylation of the acylated compound of formula (V) witha primary or secundary amine of the formula: i

the latter compound being finally reduced into a compound of formula (I)by means of aluminum lithium hydride.

Fourth process This process involves the N-alkylation of a N-substitutedaniline monohydrochloride of the formula:

in which R is a substituent, whereas n, R and R have the above meanings,by means of indanol mesylate of the formula:

/ oso CH3 (x) Fifth process:

This process involves the reaction of a N-phenyl(or2-pyridyl)-2-aminoindane of the formula (ll) (II) I A in which A and Bhave the above meanings with a bromochloroalkane of the formula Br (CH-CI in which n 2,3 or 4, so as to obtain an intermediate compound of theformula: A

which is then reacted, without isolation, with an amine of the formula(XII) The compounds of formula (II) used as starting materials in theabove described processes may be prepared by various methods Firstmethod This method involves the two following steps: l reaction of2-ceto-3-cyanoindane of the formula (XIII) CN 2 reduction of the2-phenyl (or-Z-pyridyl) amino-2- cyanoindene (XIV) into the compound offormula II by the Bouveault-Blanc method N (XIV) Second method Thismethod involves the reaction of the ester of methane sulfonic acid andthe 2-indanol of the following formula:

with aniline, a substituted aniline or Z-pyridine.

Third method This method which can be used when B represents hydrogen informula I, comprises the two following steps 1. reaction of Z-indanoneof the following formula (XVI) with aniline, a substituted aniline orZ-pyridine so as to obtain a N-phenyl (or 2-pyridyl)-2-iminoindane ofthe following formula:

N A (XVII) 2. reduction of the N-phenyl (or-2-pyridyl)-2- iminoindane bymeans of sodium borohydride.

' Fourth method When B represents a radical in the compounds of formula(I) the compounds of formula (II) wherein B represents such a radicalmay be obtained by the follow method 1. reaction of an indanol ofthe'formula:

(XVIII) OH with thionyl chloride, so as to obtain a compound of theformula v c1 (XIX) 13 2. reaction of the compound of formula (XV) withaniline. a substituted aniline or Z-pyridine In the various formulae IIto XIX. the substituents have the above meanings.

EXAMPLE 1.

- Preparation of N-phenyl-N-diethylaminopropyl-2-aminoindane and themono-anddi-hydrochlorides thereof.

A Preparation of N-phenyI-Z' aminoindane (II) a. from2-keto-3-cyanoinden'e (XIII) A mixture of 0.3 mole of 2-keto-2cyanoindene (XIII) and 0.3 mole of aniline is heated at about 95"C.

A solution is gradually obtained, whereafter the crude formed2-pheny1amino-3-cyanoinde ne(XIV) precipitates. The mixture is thencooled and recrystallized from benzene.

Analysis: Calculated: C: 82.73%; H: 5.2%; N: 12.06% Found: C: 82.4%; H:5.4%; N: 11.88%.

The obtained Z-phenylamino-3-cyanoindene(XIV) is converted intoN-phenyl-Z-aminoindane (II) by Bouveault- Blanc method.

1 part by weight of 2 -phenylamino-3-cyanoindene is placed in a reactionvesselcontaining 5O equivalents of ethanol. The mixture is boiled and,at the boiling tem-' perature, 12 parts by weight of sodium are added asquickly as possible.

When the added sodium has disappeared, the mixture is poured onto 500 gof ice. The alcohol is then evaporated as quickly as posssible and theaqueous phase is extracted with chloroform. The chloroform extract isdried on sodium carbonate, the solvent is removed and the residue isdistilled. The oil distilling at 11 1C under 0.05 mm of Hg and at139-142C under 0.05 mm of Hg is collected. 7

The collected oil is recrystallized from petroleum ether (B.P.:3032C)Yield 60%.

Analysis: Calculated: C: 86.08%; H: 7.2%; N: 6.69%. Found: C: 86.3%; H:7.3M; N:6.4%.

Melting point of the hydrochloride of N-phenyl-Z- aminoindane: l75l80C.

b. from 2-indany1 methane sulfonate (XV) 35 grams of2-indanylmethanesulfonate (XV) and 70cm of aniline are heated at 100Cwhile stirring. The reaction mixture is then cooled in order to maintainthe temperature at 100C during about minutes. At thistime, thetemperature drops and the mixture is again heated at 100C.

During the reaction, the pinkish solution thickens and becomes solid.The stirring is then stopped and the product is heated at 140C during 2minutes. A semisolid product is obtained aftercooling to room temperl4ature. This product is extracted with 1 100 cm of anhydrous ether andthe aniline methane sulfonate (byproduct) is filtered off. The ether isthen evaporated and the residue distilled.

Yield: 28.6 grams or 83%. p

c. from Z-indanone (XVI) 13.2 grams of Z-indanone (XVI) and 3.3 grams ofaniline (V) are refluxed under nitrogen within 100 ml of methanol. Aprecipitate of N-phenyLZ-iminoindane (XVII) appears after about 30minutes.

. B. Preparation of i N-phenyl-N-diethyaminopropyl-2-aminoindane and themono-and di-hydrochlorides thereof.

104.6 grams (0.5 mole) of N-phenyl-Z-aminoindane and 2.5 litres ofbenzene are introduced into a reaction vessel of 5 litres, under anatmosphere of nitrogen.

37 grams (0.95 mole) of sodium amide are added and the mixture isstirred during 3 hours at room temperature.

1 19.7 grams (0.8 mole) of -y-chloropropyl diethylamine are then quicklyadded. After agitation during 1 hour at room temperature, the reactionmixture is refluxed and stirred undernitro'gen during 21 hours. The

mixture is then allowed to cool and poured onto ice. The obtainedaqueous phase is extracted by means of 500 cm of benzene.

The benzene extract is washed two times with 200 cm of water and thebenzene is then evaporated.

The residue is treated with 500 cm of hydrochloric acid (2 N). Theobtained solution is evaporated to dryness and the oily residue isrecrystallized from ethanol. 176.9g (Yield: 89.4%) of dihydrochloride ofN-phenyl- N-diethylaminopropyl-2-aminoindane are obtained.

Melting point: 208210C.

The dihydrochloride'is converted into monohydrochloride by dissolving26.36 grams (0.066 mole) of dihydrochloride into 158 cm cm of water,adding .drop

1 by drop a suitable amount (0.066 mole) of caustic soda 1N),evaporating the aqueous solution to dryness. drying by means of benzene,filtering the formed. sodium chloride (3.8 grams) and crystallizing thecooled obtained benzene solution. 22.6 grams ofmonohy drochloride areobtained. Melting point: l20-l2lC.

Analysis:

a. dihydrochloride.

Calculated: C:66.827(; H:8.l5%'. N:7.087(; Cl 17.9%. Found: C 65.83%;H:8.l972; N:7.27'7c; b. monohydrochloride EXAMPLE 2.

Preparation of N-phenyl-N-dimethylaminopropyl-2-aminoindanemonohydrochloride (formula 1; A phenyl; R =R =CH ;n=2: Z H B Thiscompound is prepared as described in example 1, except thaty-chloropropyl dimethylamine is used in place of y-chloropropyldiethylamine.

The monohydrochloride of N-phenyl-N-dimethylaminopropyl-Z-aminoindane,obtained with a yield of 85%, melts at ISO-153C.

EXAMPLE 3.

Preparation N-phenyl-N-dipropylaminopropyl-2-aminoindane and thedihydrochloride thereof This compound is prepared as described inexample 1. except that 'y-chloropropyl dipropylamine is used in place ofy-chloropropyl diethylamine. The amine obtained with a yield of 75% hasa distillation temperature range of 172-l75C under 0.85 mm of Hg.

Analysis: of the dihydrochloride -M.P. l75 177C (czflggoH- ethelfiCalculated: C: 68.07; H:8.57%; N:6.6.%; Cl:16.74%. Found: C: 68.69;H:8.7%; N: 6.36%; Cl: 16.20%.

EXAMPLE 4.

Preparation of N-phenyl-N-diethylaminoethyl-Z-aminoindane and themonohydrochloride thereof.

(formula 1; Aahenyl; R =R C H n 1; Z H B H).

This compound is prepared as described in example 1, except hasB-chloroethyl diethylamine is used in place of 'y-chloropropyldiethylamine.-The amine obtained with a yield of 90% has a distillationtemperature range of l85-l90C under 1 mm of Hg.

Analysis: of the monochydrochloride -M.P.: 127- 129C (CHCl ether and C HOH ether) Calculated: 073.12%; H:8.4%; N:8.l%; Cl:lO.3%. Found: C:72.8%;H:8.78% N:8.06%; Cl:l0.03%.

EXAMPLE 5.

Preparation of N-phenyl-N-dimethylaminoethyl-Z-aminoindane and themonohydrochloride thereof.

This compound is prepared as described in example 1, except thatB-chloroethyl dimethylamine is used in place of y-chloropropyldiethylamine. The amine obtained with a yield of 65% has a distillationtemperature range of 153C under 0.4 mm of Hg.

Analysis: of the monohydrochloride -M.P.:2 l52 1 7C (anhydrous C H OH)Calculated: c:72.01%; n;7.95'%; N:8.84%; c1; 11.19%. Found: C:7l.09%;H:8.0l%; N:8.98%; Cl: 11.08%.

EXAMPLE 6.

Preparation of N-phenyl-N-piperidinoethyl-Z-aminoindane and themonohydrochloride thereof (formula 1; A=phenyl;

\R I I pipcridino;

Calculated: C: 74.02%; H:8.l9%; N:7.85%; Cl:9.9.%. Found: C:74.43%;H:8.54%; N:7.7%; Cl: 9.52%.

EXAMPLE 7.

Preparation of N-phenyl-N-morpholinoethyl-2-aminoindane and themonohydrochloride thereof (formula I; A=phenyl;

N m orpholino;

This compound is prepared as described. in example 1, except thatB-chloroethyl morpholine is used in place of 'y-chloropropyldiethylamineJThe amine obtained with a yield of 86.5% has a distillationtemperature range of 178l84C under 0.45 mm of Hg.

Analysis: of the monohydrochloride 199.5-202.5C (11 Calculated:C:70.27%; H:7.58%; N:7.8%; Cl:9.87%..

Found: C:70.26%; l-l:7.52%; Cl:9.72%.

EXAMPLES 8 TO 14 Preparation of N-phenyl-substitutedphenyl-N-diethylaminopropyl-Z-aminoindanes (formula I; A= substitutedphenyl; R,=R CZH n=2; Z=H- B=H) a. Preparation of N-substitutedphenyl-2-aminoindanes A series of N-substituted phenyl-Z-aminoindaneshave been prepared by the method described in example 1, a,b, using asubstituted aniline in place of unsubstituted aniline.

The following table shows the melting point of the obtained compoundsand of the hydrochlorides thereof.

' TABLE 2 substituent Melting Molecular Melting of the point weightpoint of phenyl ring "C hydrochloride 2-Cl 59-60 243.73 182 184 3-C142-43 243.73 158 164 4C1 98-100 243.73 2CH 63-65 223.30 215 217 3-CH,,72-74 277.27 213 215 4-OCH; 64-66 239.29 179 182 2-6CH -CH 63-65 237.32

B. Preparation of N-substituted phenyl-N-diethy1aminopropylZ-aminoindanes.

A series of N-substituted phenyl-N-diethylaminopropyI-Z-amirioindaneshave been prepared by the method described in example 1, B from theN-substituted phenyl-Z-aminoindanes of Table I. The following table 11shows the melting point of the indicated acid addition salts obtained bysaid process, as well as the analytical data of the obtained compounds.

EXAMPLE 15 Preparation of N-9-hydroxyphenyl )-N-y-diethylaminopropyl)-2- aminoindane dihydrochloride EXAMPLE 16 Preparation ofN-(2,6-dichloropheny1)-N-(y-diethylaminopropyl)-2- aminoindanemonohydrochloride (formula I: A 2,6-dichlorophenyl; R, R C H n= 2; Z H BH) A. Preparation of N-(2,6- dichlorophenyl)-2-aminoindane 2.12 g of2-indano1 mesylate, 12.96g of 2,6- dichloroaniline and 40 ml of tolueneare refluxed during 24 hours. The toluene phase is then washed withwater, dried and evaporated. By distillation 0.02g of an oil areobtained at C under a pressure of 0.02 mm.

Analysis: Calculated: C: 64.76%; H:4.71%; N:5.04%; Cl:25.49%. Found: C:64.4%; H:4.6%; N:4.99%; CI: 25.8%.

B. Preparation of N-( 2,6-dichlorophenyl )-l\l-( ry diethylaminopropyl)-2 aminoindane monohydrochloride 21 .35g of N-( 2,6-dich1orophenyl)-2-aminoindane. 14.3 ml of y-chloropropyldiethylamine, 4.6g of sodiumamide (NaNH and 250 m1 of benzene are refluxed during 8 hours.

From the obtained mixture, the monohydrochloride is prepared in theusual way. After recrystallization from benzene (U3) and cyclohexane(2/3), the desired monohydrochloride melts at 138.3C

Analysis: Calculated: C:6l..8%; 1-1: 6.4%; N:6.55%; C1 25.19%. Found:C:6l.76%; H: 6.82; N:6.55%; C1:

TABLE 3 Example Substitucnt of Acid addi- Melting Molecular Analysis.

the phenyl ring tion salt point "C weight.

8 2--Cl fumarate 126-128 473:00 Cal.C:66.01;H:7.03;N:5.92;Cl7.49%

Found:C:65.90;H:7.07;N'6 00;C17.52%

10 4-C1 fumarate 138-140 473.00 Ca1.C:66.01;H:7.03;N:5.92;Cl.7.49%

Found:C:65.98'.l-l.7.l l:N:6.0l;Cl.7.60%

ll 2CH; fumarate 115-117 45256 Cal.C:7l.65;H.8.01:N:6.18%

Found:C:71.7l ;H.7.98;N:6.20%

l2 3 CF fumaratc 105-107 506.54 Cal.C:64.0l :H.6.56;N:5.52%

Found:C:64.l3;H.6.48:N:5.48%

l3 4-OCH oxalate -128 442.53 Cul.C:67.85-.H:7.74;N11.32%

Found:C:67.78;H:7.72;N:6.41%

14 2--6C1-1 oxalate -160 440.55 Cal.C:70.87;H:8.23;N:6.41%

EXAMPLE 17.

Preparation of N-phenyl-N-[ 4-methylpiperazino )-propyl]-2- aminoindane(formula 1; A phenyl;

R, N melthylpipcrazino A Preparation ofN-phenyl-N-B-chloropropionyl-Z-aminoindane 0.04 mol ofN-phenyl-Z-aminoindane are acylated by means of 0.06 mol of the chlorideof B-chloropropionic acid in 50 ml of benzene. After reflux heatingduring 5 hours, the solvent is evaporated and the residue isrecrystallized from petroleum ether. The obtained product melt at 85C.

Analysis Analysis: C: 42.11; H:6.05; Cl: 11.8%. Found: C: 72.39; H:6.0l;Cl: 11.82%.

B Preparation of N-phenyl-N-y-chloropropyl-2-aminoindane hydrochloride.

A solution of 45g of the acylated product obtained as described under ahereabove in 1000 ml of ether is added drop by drop to a mixture of 500ml of ether and 8.7g of lithium-aluminum hydride (AlLiH at roomtemperature. After this addition, the reaction mixture is refluxedduring 2 hours.

By extraction by means of ether, an oil is obtained (41 g), which isconverted into the hydrochloride by passing a stream of dry hydrochloricacid through an ether solution of the product. Crystals melting at144l46C are obtained.

Analysis: Calculated: Cl 22%. Found: Cl 21.57%.

C. Preparation of N-phenyl-[ 4-methylpiperazino )-propyl]-2-aminoindane6.44 g of N-phenyl-N-p-chloropropyl-2-aminoindane and 15.84g 17.6 ml) ofN-methylpiperazine are refluxed in 50 ml of ethanol during hours. Theethanol and the excess of methylpiperazine is then evapored and theresidue is treated with water and subsequently extracted with petroleumether. After drying and evaporation of the organic phase, a residue (7g)is obtained, which is converted into the hydrochloride at a.pH of 6. Thehydrochloride (6.5g) is extracted by means of dichloromethane andrecrystallized form methylethylketone, M.P:156158C Analysis: Calculated:C:71.57%; H:8.36%; N:10.89%; Cl:9.13%. Found: C:71.49%; H:8.20%;N:10.91%; C1:9.21%.

EXAMPLE 18.

Preparation of N-phenyl-N-( S-diethylaminobutyl)-2-aminoindane (formula1: A phenyl; R, R C H n 3; Z H2; B H) a. Preparation ofN-phenyl-N-y-chlorobutyroyl-2-aminoindane.

53ml (0.4 mol) of the chloride of 'y-chlorobutyric acid are added dropby drop, at a temperature of 20C, to a solution of 41 .86g of2-phenylaminoindane in 270 ml of benzene. The mixture is refluxed during2 hours and then concentrated to dryness. The oily residue is washedwith petroleum ether (B.P.: 40 60C) and the insoluble oil iscrystallized from cyclohexane. M.P. 76- 77C. 7

Analysis: Calculated: .C: 72.41 H:6.42 N:4.46 Cl:11.30 Found: C: 72.73H:6.37 N:4.64 Cl:

B. Preparation of N-phenyl-N-( y-diethylaminobutyrol)-2-aminoindane l9(0.062 mol) of N-phenyl-N-('y-chlorobutyrol)- 2-aminoindane, 28 ml ofdiethylamine and ml of ethanol are heated in an autoclave at C during 24hours. After cooling and evaporation, the residue is treated with a 1Ncaustic soda solution and extracted with benzene.

The obtained product is purified by converting it in oxalate. The purerecovered base is crystallized from a mixture of methylethylketone andmethanol. M.P.: l21-122C Analysis: Calculated: C: 68.16%; H: 7.32%; N:6.36%; C1: 18.16%. Found: C: 68.03%; H: 7.04%; N: 6.53%; C11.

C. Preparation of N-phenyl-N-( 8-diethylaminobutyl )-2-aminoindane Asolution of 13.5 g of N-phenyl-N-(y-diethylaminobutyroyl)-2-aminoindanein 200 ml of ether is added to 300 ml of ether containing 3.25g of Al LiH The mixture is refluxed during 4 hours and, after cooling, 50 ml of'water are added thereto. The separated ether phase is washed withwater, dried and evaporated.

10.7g of an oil are obtained. This oil is treated with 50 ml of waterand 32 ml of 1N hydrochloric acid. The acid phase is extracted withpetroleum ether and with dichloromethane. The oil (12.5g) obtained afterevaporation of the dichloromethane is recrystallized from ethylaccetate. M.P. 124125C (hydrochloride) Analysis: Calculated: C: 74.06%;H:8.92%; N: 7.51%; Cl: 9.51%. Found: C: 74.69%; H:8.48%; N: 7.72%: Cl:

EXAMPLE 19.

Preparation of N-phenyl-N(piperidinobutyl)-2-aminoindane (A phenyl;

R e N R0 I) pipcridino;

n=3:Z=H ',B=l-l 2.24g of N-phenyl-N(-5-chlorobuty1)2-aminoindane, 4.54g(5.3 ml) of piperidine and 50 ml of anhydrous ethanol are heated at 100Cin an autoclave during 24 hours. After cooling and evaporation, theresidue is treated with water and made alkaline (pH 1 1). Afterextraction with benzene, washing drying and evaporation of the benzene,an oily residue is obtained.

This residue is treated with 1N hydrochloricacid and extracted by meansof dichloromethane. The acid aqueous phase is brought to a ph of 6 andextracted by means of dichloromethane. The obtained monoh ydro chlorideis recrystallized of a mixture of methylethylketone and methanol. M.P.170C Analysis: Calculated: C: 74.87%; H: 8.64%; N: 7.28%; Cl: 9.21%.Found: C: 74.75%;H: 8.55%; N: 7.34%; Cl: 9.29%. 7

EXAMPLE 20 Preparation of N-phenyl-N-( B-diethylaminopropyl)-2-aminoindane hydrochloride (formula 1: A phenyl; R f R B Preparationof N-phenyl-N-( oz-diethylaminopropionyl )-2-aminoindane 18.54 g (0.062mol) of N-phenyl-N-(a'chloropropionyl)-2-aminoindane, 60 ml of anhydrousethanol and 21 ml of diethylamine (0.19 mol) are heated at 120C in anautoclave during 24 hours.

By recrystallization of the residue obtained by concentration to drynessfrom petroleum ether (B.P. 4060C) the desired product melting at 74-75Cis obtained.

Analysis: Calculated: C: 78.53%; H: 8.39%; N: 8.33%. Found: C: 78.44%;H. 8.55%; N: 8.60%.

C. Preparation of N-phenyl-N-.(B-diethylaminopropyl)-2-aminoindanehydrochloride 9.85g of N-phenyl-N-(a-diethylaminopropionyl)-2-aminoindane and 150 ml of ether are added drop by drop to a suspensionof aluminum lithium hydride. in 100 ml of ether.

The obtained mixture is refluxed during 4 hours and 35 ml of water areadded after cooling. The ether phase is then evaporated and the residueis treated with 1N hydrochloric acid.

The obtained acid phase is extracted successively with petroleum etherand dichloromethane. The residue from the dichloromethane phase isrecrystallized from ethyl acetate. M.P. 158-160C Analysis: Calculated:C: 73.61%; H: 8.70%; N: 7.81%; Cl: 9.88%. Found: C: 73.75%; H: 8.60%; N:7.86%; Cl: 10.15%.

EXAMPLE 2 1 Preparation of N-phenyl-N-( 'y-dihydroxyethylaminopropyl)-2- aminoindane (formula 1; A phenyl; R, R hydroxyethyl: 1E2; Z H B H)A. Preparation of N-phenyl-N-( B-dihydroxyethylaminopropionyl )-2-aminoindane 6.93 g of N-phenyl-N-(,B-chloropropionyl)-2- aminoindane and14 ml of dihydroxyethylamine are heated on a water-bath during 30minutes After dilution by water. the reaction mixture is made acid.

The obtained solution is treated with charcoal and filtered. Thefiltrate is concentrated to dryness and the residue is recrystallizedfrom isopropanol M.P. 130.l31C

Analysis: Calculated: C: 65.25%; H: 7.22%; N: 6.92; C]: 8.76%. Found: C:65.26%; H: 7.17%: N: 7.10%: Cl: 8.9%. i

B. Preparation of N-phenyl-N-(a-dihydroxyethylaminopropyl)-2-aminoindane fumarate 5.2g ofN-phenyl-N-(,B-dihydroxyethylaminopropionyl)-2-aminoindane are reducedby means of lithium aluminum hydride in ether by refluxing the mixtureduring 3 hours. The separated product is converted into thecorresponding fumarate which is recrystallized from ethanol. M.P.l37138C Analysis: Calculated: C: 66.36%; H: 7.28%; N: 5.95%. Found: C:66.28%; H: 7.23%; N: 6.00%.-

EXAMPLE 22.

Preparation of N-pheny1-N-(y-dialkylaminopropyh- 2-aminoindanemonohydrochloride (formula 1; A phenyl; R R allyl; n 2; Z H B H) 6.44gof N-phenyl-N-('y-chloropropyl)-2-aminoin dane, 15.54g of diallylamineand 50 ml of ethanol are heated at C in an autoclave during 24 hours.

The reaction mixture is treated in the usual way, so as to obtain -themonohydrochloride which melts at 138l 39C after recrystallization frommethylethylketone.

Analysis: Calculated: C: 75.26%; H: 8.16%; N: 7.31%; Cl: 9.26%. Found:C: 75.22%; H: 7.97%; N: 7.24%; C]: 9.08%.

EXAMPLE 23 ml of anhydrous triethylamine and 200 ml of benzene arestirred during 1 hour at room temperature. After addition of 50 ml ofwater, the benzene phase is de- 23 canted by means of 100 ml of water,dried and evaporated.

An oily residue (9g) is obtained. By recrystallization from petroleumether (B.P. 4060C) a solid melting at 47-49C is obtained Analysis:Calculated: C: 78.81%; H: 8.63%; N: 7.99%. Found: C: 78.75%; H: 8.65%;N: 8.00%.

B. Preparation of N-phenyl-N-[y-N'-ethyl-N'-propyl) aminopropy1]-Z-aminoindane monohydrochloride 1.5g ofN-phenyl-N-[(y-N'-ethyl-N-propionyl) aminopropyll-2-aminoindanedissolved in 70 ml of ether are added drop by drop to a suspension of0.35g of lithium aluminum hydride in 120 ml of ether.

The obtained cooled mixture is refluxed during 3 hours.

The desired monohydrochloride is obtained by the usual extractionmethod. The oily residue obtained by extraction from the aqueous phaseat a pH of 6, by means of dichloromethane is recrystallized fromethylacetate. M.P. 107l08C.

Analysis: Calculated: C: 74.06%; H: 8.92%; N: 7.51%; Cl:9.5l%. Found: C:74.01%; H: 8.85%; N: 7.25%; Cl:9.64%.

EXAMPLE 24 Preparation of N-pheny1-N-('y-N-methyl-N'-ethylaminopropyl)-2- aminoindane monohydrochloride (formula I; A phenyl; R; CH R 11 n 2;Z H2; B H) 6.44g (0.02 mol) pf N-phenyl-N-('y-chloropropyl)-2-aminoindane hydrochloride, 9.44 g (0.16 mol) of methylethylamine and 50ml of ethanol are heated at 100C in an autoclave during 24 hours. Afterevaporation to dryness, the mixture is treated with a 0.1 N sodiumhydroxide solution. The obtained mixture is extracted withdichloromethane. washed and dried. By evaporation of thedichloromethane. 6.3g of a residual oil are obtained. Themonohydrochloride prepared from this oil and recrystallized in ethylacetate melts at l26--127C Analysis: Calculated: C: 73.12%; H: 8.48%; N:8.12%; Cl: 10.28%. Found: C: 73.01%; H: 8.53%; N: 8.21%; Cl: 10.57%.

EXAMPLE Preparation of N-phenyl-N('y hydroxyethyl-ethylaminpropyl-2-aminoindane monohydrochloride A. Preparation of N-phenyl-N,B-hydroxyethyl-ethylaminopropionyl )-2- aminoindane monohydrochloride20 g of N-phenyl-N-(B-chloropropionyl)-2aminoindane, 17.83g (19.6 ml 0.2mol) of ethylethanolamine and 100 ml of ethanol are refluxed during'24hours.

After evaporation of the volatile materials, 150ml of a 0.1 N sodiumhydroxide solution are added and the mixture is extracted with benzene.The residue of the benzene solution is dissolved in ether, a stream ofgaseous hydrochloric acid being then passed through the ether solution.After recrystallization from methylethylketone, the desiredhydrochloride melts at 9095C.

24 Analysis: Calculated: C: 67.93%; H: 7.52%; N: 7.20%; Cl: 9.11%.Found: C: 68.12%; H: 7.64%; N: 7.50%; Cl: 9.17%.

B. Preparation of N-phenyl-N-(y-hydroxyethyl-ethylamino)propylZ-aminoindane monohydrochloride TheN-phenyl-N-('y-hydroxyethyl-ethylamino)-propionyl-2-aminoindanemonohydrochloride is reduced by means of lithium aluminum hydride. Thedesired product recrystallised from ethylmethylketone melts at 98100CAnalysis: Calculated: C: 70.47%; H: 8.53%; N: 7.47%; Cl: 9.45%. Found:C: 70.55%; H: 8.10%; N: 7.52%; Cl: 9.42%.

EXAMPLE 26 Preparation of N-phenyl-N-( 5-methyl-propyl-amino-butyl )-2-aminoindane oxalate (formule l: A phenyl; R =CH R =C H n 3; Z 2; B

6 g (0.02 ml) of N-phenyl-N-(8-chlorobutyl)-2- aminoindane, 3.75g (0.05mol) of methyl-propylamine and 50 ml of anhydrous methanol are refluxedunder nitrogen during 24 hours. After cooling and evaporation of thevolatile materials, 100 cc of a 0.1 N solution of sodium hydroxyde areadded and the obtained mixture is extracted with dichloromethane. Theextract is dried and evaporated. The residue is treated with 40 ml of 1Nhydrochloric acid and the mixture is extracted with dichloromethane. Theobtained extract is evaporated, brought to be pH of 6 and againextracted with dichloromethane.

After evaporation, an residual oil is obtained which is converted intoan oxalate. The oxalate recrystallized from a mixture of ethyl acetateand methanol melts at l54-157C.

Analysis: Calculated: C: 70.39%; H: 8.13%: N: 6.57%. Found: C: 70.67%;H: 8.02%; N: 6.70%.

EXAMPLE 27' Preparation of1-methoxy-2-[N-pheny1-N-(diethylarninopropyl)]- aminoindane (formula I:A phenyl; R =R =C H n 2; Z H

A. Preparation of mesylate of l-methoxy-2-hydroxyindane Analysis:Calculated: C: 54.54%; H: 5.82%. Found: I

B. Preparation of 1-methoxy-2-phenylaminoindane 60.5g of the mesylateobtained in section A and ml of aniline are heated during 3 hours at C.The reaction mixture is then cooled and extracted by means of 150 ml ofether. After separation of the precipitated aniline mesylate byfiltration, the ether is removed from the filtrate and the filtrate isdistilled. The desired product distils at l65C/0.05 mm. The distilledproduct becomes solid and is recrystallized from isopropanol. Meltingpoint: 53-54C.

Analysis: of the hydrochloride melting at 182184C and recrystallizedfrom acetone.

Calculated: C: 69.68%; H: 6.58%; N: 5.07%; C]: 12.85%. Found: C: 69.65%;H: 6.55%; N: 5.18%; Cl: 12.68%.

C. Preparation of l-methoxy-2-[N-phenyl-N-( diethylaminopropylaminoindane.

A mixture of 1.2 g (0.03 mol.) of NaNH 30 ml of toluene and 0.015 mol.of l-methoxy-2- phenylaminoindane is boiled during 30 minutes. 3.75 g ofy-chloropropyldiethylamine are then added and the mixture is refluxedduring 3 hours. After cooling and addition of 50 ml of water, thetoluene phase is separated, dried and concentrated, so as to obtain aresidue (6.3g) which is treated with 2 grams of fumaric acid and 50 mlof water. The obtained solution is evaporated under vacuum and theresidue is treated by means of 50 ml of ether. A solid product isobtained. After recrystallization from acetone or a mixture of acetoneand methanol, 4.4 g of a product melting at 138-140C are obtained.Yield: 63%

Calculated: C: 69.2%; H: 7.74%; N: 5.97%. Found: C: 69.2%; H: 7.38%; N:6.12%.

EXAMPLE 28 Preparation of 1-ethoxy-2-/N-phenyl-N-(diethylaminopropyl)/-aminoindane (formula 1: A phenyl; R =R C H n 2; H B O CH A. Preparationof l-ethoxy2-hydroxyindane 5 g of Na are dissolved in 140 ml of ethanol.To the obtained solution 423g of l-hydroxy-Z-bromoindane are added. Themixture is refluxed during 19 hours under nitrogen. 100 ml of ethanolare removed by distillation and 200 ml of ether .are added. Aftercooling, the sodium bromide is separated by filtration and the ether isevaporated. The desired product is obtained by distillation at8790C/0.05mm. Yield: 25.4 g (71%).

B. Preparation of the mesylate of 1-ethoxy-2-hydroxy-indane 0.07 mol ofl-ethoxy-Z-hydroxyindane and 0.105 mol (10.6 grams) of distilledtriethylamine are dissolved in 60 ml of anhydrous dichloromethane. 0.077mole (8.82 grams) of CH SO CI are then added drop by drop to thesolution which has previously been cooled to 5C. The mixture is thenstirred during 30 minutes at room temperature. The reaction mixture isdiluted with 60 ml of dichloromethane and the obtained solution issuccessively washed with hydrochloric acid (100 ml at 0C), with asaturated solution 1 of sodium bicarbonate (30 ml at 0C) and with asaturated aqueous solution. of sodium chloride (50 ml at 0C). Theorganic phase is then dried and evaporated. 16.17 grams (94%) of aresidue meltingat 5657C after recrystallization from isopropanol areobtained.

26 Analysis: Calculated: C: 56.23%; H: 6.29%; S: 12.51%. Found: C:56.6%: H: 6.27%; S: 12.42%.

C. Preparation of 1-ethoxy-2-pheny1aminoindane 60.5 g of the mesylateobtained in section B of example 28 and 125 m1 of aniline are heatedduring 45 minutes at 150C. After cooling, the mixture is treated with150 ml of ether and the formed aniline mesylate is separated byfiltration. The ether is removed from the filtrate and the excess ofaniline is distilled. The residue of this distillation is treated with 6N hydrochloric acid, so as to obtain the hydrochloride which isextracted by means of chloroform. The obtained solution is dried onsodium sulfate, filtered and concentrated to dryness. By addition ofacetone 19.77 grams (yield 56%) of the hydrochloride melting at l72173Care obtained. After recrystallization from a mixture and methanol, thehydrochloride melts at 176C.

Analysis of the hydrochloride: Calculated: C: 70.45%; H: 6.96%; N:4.83%; C1: 12.24%. Found: .C: 70.85%; H: 6.88%; N: 5.0%; Cl: 12.1%.

The free base melts at 7172C and is recrystallized from isopropanol.

'Analysis of the base: Calculated: C: 80.59%; H: 7.66%; N: 5.53%. Found:C: 80.35%; H: 7.42%; N: 5.41%.

D Preparation of 1-ethoxy-2-[N-phenyl-N-(diethylaminopropyl aminoindaneThis compound is prepared by the method used in section C of example 27,using l-ethoxy-2- phenylam inoindane instead of l-methoxy-2-phenylaminoindane. The duration of the reaction is 22 hours and theyield of 20%. The oxalate recrystallized from isopropanol melts atl33-l34C.

Analysis: Calculated: C: 68.39%; H: 7.95%; N: 6.14%. Found: C: 68.2%; H:7.74%; N: 6.05%.

EXAMPLE 29 Preparation of 1-methoxy-2[N-phenyl-N-(dimethylaminopropyl)-]aminoindane (formula I: A= phenyl; R R CH n 2; Z H B OCH;,)

This compound is prepared by the method described in the example 27,section C, using y-chloropropyldimethylamine instead ofy-chloropropyldiethylamine. The duration of the reaction is of 4 hours.Yield:

The fumarate of the desired compound is recrystallized from acetone.Melting point 149 151C Analysis: Calculated: C: 68.16%; H: 7.32%; N:6.36. Found: C: 68.00%; H: 7.20%; N: 6.43%.

EXAMPLE 30 Preparation of 1-methoxy-2- N-phe nyl-N-( diethylaminoethylaminoindane (formula I; A phenyl; R R C H n 1; Z

A. Preparation of l-metho xy-2-( N-phenyl-N-chloracetyl )-aminoindane0.04 mol of 1-methoxy2-phenylaminoindane and 0.06 mol of ClCO'CHgCl arerefluxed in benzene (50 ml) during minutes. After cooling, the benzeneis removed. The residue is washed with 20 ml of petro- 27 28 leum etherand recrystallized from petroleum ether. Melting point lO4lO5C. Yield:95% EXAMPLE 32 Analysis: Calculated: C: 68.46%; H: 5.74%; N: Preparation9 4.43%; (:1; 11.23%. Found: c; 69.11%; H: 5.59%; N: y- -1 -p -(p p yll- 5 aminoindane B. Preparation of (formula I i A phenyl;

l-methoxy-2-[N-phenyl-N-diethylaminoacetyl aminoindane 0 N piperidim;5.8 g of 1-methoxy-2-(N-phenyl-N-chloracetyl)- aminoindane and 2.63g ofdiethylamine are dissolved in 50 ml of anhydrous ethanol. The solutionis refluxed Z=H2 during 24 hours, but after 6 hours 1.32 grams ofdiethpreparation f ylamine are still added. When the reaction isfinished, 1 methoxy 2 (N phenyLNPiPeridinoacetYl) aminoin the alcohol isremoved and the residue is treated with dane diluted hydrochloric acid.The obtained solution is made alkaline and extracted by means ofchloroform. After removal of the chloroform a residue of 6 g is ob- Thiscompound is prepared in the manner described in example 30, section B,except that piperidine is used instead of diethylamine.

tained. After recrystallization fom acetone, the hydro- The Obtainedfree amine melts at 85 86C Yield chloride melts at l88l90C 75% iAnalyslsz Calculated: C: 679476; H: 751%; N: 720; The hydrochloride ofthe amine'recrystallized from 512897.11. Found: C: 68%: H: 7.48%; N:6.98%; Cl: aaetone melts at 6 C' Preparation of Analysis of theHydrochloride: C H N Cl 1-methoxy-2-[N-phenyl-N-(d1ethylam1noethyl)]- II t d 68 9 7 79 698 8 84 L CH CH d C t lmmomdane found 69.07 7.03 7.208.96

The compound prepared in example 30, section B, is reduced by means ofaluminum lithium hydride by a known method. The hydrochloride of thedesired com- B Preparation of Pound melts at IMO-147C1-methoxy-2-[(N-phenyl-N-(piperidinoethyl)- 3 ]amin0indane.

This compound is prepared from 1-methoxy-2-(N-phenyl-N-piperidinoacetyl)-aminoindane by reduction by means of aluminumlithium hydride. The fumarate Preparation ofl-methoxy-2-[N-phenyl-N-(diethylaminopropyl)]- aminoindanerecrystallized from ethyl acetate melts at 140142C. (formula I; Aphenyl; R =R =C H n 2; Z H B OCH Analysis: C H N A prgparauon ofcalculated: 69.5 7.34 6 l-methoxy-2-(N-phenyl-N-fi-chloroproplonyl)- 7,round; 69.7 7 32 5.93

aminoindane monohydrochloride This compound is prepared as described inexample 30, section A, using the chloride of ,8chloropropionic EXAMPLE33 acid instead of the chloride of chloroacetic acid. Yield: Preparationof 90%. The desired product melts at l17-l18C after l dimethylamino z[(N phenyl N (,y diethylamino recrystallization form petroleum ether (6080C). propyl) am-moindane Analysis: Calculated: C: 61.19%; H: 6.11%; N:4.25%; c1; 10.75%. Found: c: 64.9%; 1-1: 6%; N: 4.35%; i q PhenyhRFRFCEH-a Z412, Cl: 106070 B-d1met y ammo).

A. Preparation of B. Preparat1on of 1l-methoxy-2-(N-phenyl-N-diethylaminopropionyl)- 1 dlmethylammO2-phenylammOmddne aminoindane 1 1.2 g of 1-dimethylamino-2-chloroindanehydrochloride are stirred during 2 hours at room temperature Thlscompound prepared m the manner descnbed in 40 ml of aniline. Thereaction mixture is treated by m example Sectlon 6 means of ml ofchloroform and the aniline hydro- C. Preparation of 1-methoxy-2-(N-phenyl-N-diethylaminopropyl aminoindane monohydrochloride rated todryness, so as to remove the excess of aniline. The residue is treatedwith 250 ml of water. After addition of charcoal, the solution isfiltered and made alka- Thls compound is P p y reduction of 65 line. Bycooling in a refrigerator, the desired amine is methoxy-2-(N-phenylobtained (11.5 g; Yield: 95%). After recrystallizationN-diethylaminopropionyl)-aminoindane by means of from petroleum ether(6080C) the product melts at aluminum lithium hydride. 92C.

chloride is separated by filtration. The filtrate is evapo- I Analysis:C H N a calculated: 80.91 7.93 11.1 /1 found: 81.40 7.91 ll.25 Analysisof the fumaratc: C H N 7( calculated: 68.46 6.56 7.6 l2 found: 68.846.6l 7.57

C H N "/1 calculated: 64.77 7.65 8,39 '7: found: 64.66 7.73 8.05

EXAMPLE 34.

Preparation of 1-dimethylamino-2- N-phenyl-N-('y-dimethylaminoprpyl)]-aminoindane (formula I A=phenyl; R,=R =Cl-l n=2;Z=H B=dimethylamino).

This compound is prepared in the manner described in example 27, sectionC, from 3) l-dimethylamino-2- phenyl-aminoindane by using'y-chloropropyldimethylamine as alkylating agent. The preparedPreparation (yield 80%) melts at 193-195C. From the puritied oxalate,the free amine is prepared and converted into difumarate which melts atl67-l69C after recrystallization from acetone and methanol.

Analysis: Molecular weight 569.66 (C H N oxl C H N '71 calculated: 63.256.9 7.37 71 found: 63.2! 7.19 7.38

EXAMPLE 35.

Preparation ofl-dimethylamino-2-[N-metachlorophenyl-N-(y-diethylaminopropyl]-aminoindane (formula I R,=R- =C H n 2; Z=H B=dimethylamino;A=m-chlorophenyl).

A. Preparatin of ldimethylamino-Z-m-chlorophenylaminoindane.

3 g of l-dimethylamino-2-chl0roindane hydrochlo-v ride and ml ofmetachloroaniline are stirred during 3 hours at room temperature. Afteraddition of 50 ml of chloroform, the metaehloroaniline hydrochloride isfiltered. The filtrate is evaporated to dryness and the residue istreated with water so as to obtain a'solution. 3.2 g of thehydrochloride of the desired product are obtained (yield: 76%). Byrecrystallization from acetone, the monohydrochloride melts at 230-232C.

Analysis: C H N Cl /1 calculated: 63. i6 6.23 8.66 21.93 "/1 found: 63.56.37 8.66 22.1

The corresponding free base melts at 69-72C.

B. Preparation of l-dimethylamino-2-[N-metachlorophe- 4 nyl-N-('y-diethylam inopropyl l-aminoindane.

This compound is prepared in the manner described in example 27, sectionC, using l-dimethylamino-Z-mchlorophenylaminoindane instead of1-methoxy-2- phenylaminoindane. Benzene is used as solvent and theduration of the reaction is 2 hours. The yield is 80%. The oxalateobtained by recrystallization from acetone and methanol melts at l86l87C.

Analysis of the oxalate: Molecular weight:580.08

C H N Cl /1 calculated: 57.97 6.6 7.24 6.1 l A found: 5815 6.7 7.39 6.28

The fumarate obtained by recrystallization from ethanol melts atl46148C.

Analysis of the fumarate:

C H N Cl 7! calculated: 60.80 6.69 6.64 5.6

% found: 60.65 6.48 6.44 5.35

EXAMPLE 36.

Preparation of l-dimeth ylamino- 2- N p-methoxyphenyl )-N-('y-diethylaminopropyl ]-aminoindane (formula I R =R =C H n 2; Z=HB=dimethylamino; A p-methoxyphenyl).

A. Preparation of l-dimethylamino-Z-p-methoxyphenylaminoindane.

8 g of l-dimethylamino-2-chloroindane and 8.8 g of para anisidine arestirred during 15 hours at room temperature. The p-anisidinehydrochloride is filtered. The filtrate is evaporated to dryness andrecrystallized from acetone. Yield: 50%. Melting Point: 213 2l5C.

Analysis of the monohydrochloridc.

C H N C] '7: calculated: 67.8 7.27 8.78 ll.ll /r found: 67.63 6.87 8.79ll.33

B. Preparation of 1-dimethylamino-2-[N-(p-methoxyphenyl )-N-('y-diethylaminopropyl j-aminoindane.

This compound is prepared in the manner described in example 27, sectionC, using l-dimethylamino-Z-pmethoxyphenylaminoindane instead ofl-methoxy-2- phenylaminoindane.

EXAMPLE 37.

Preparation of1-ethylamino-2-[N-phenyl-N-('y-diethylaminopropyl)]-aminoindane.

A. Preparation of l-ethylamino-2-phenylaminoindane.

Analysis: C H N 7: calculated: 80.91 7.99 1 1.09 "/1 found: 80.86 7.9611.40

B. Preparation of l-ethy1amino-2-[N-phenyl-N-(y-diethylaminopropyll-aminoindane.

This compound is prepared in the manner described in example 27, sectionC, using l-ethylamino-Z- phenylaminoindane instead of l-methoxy-Z-phenylaminoindane.

EXAM PLE 3 8.

Preparation of l-methylamino-2-[ N-phenyl-N-( y-diethylaminopropyl-aminoindane.

(formula 1 B=methy1amino; A=phenyl; 71 2; Z=H R,=R ethyl).

A. Preparation of l-methylamino-2-phenylaminoindane.

This compound is prepared in the manner described in example 37, sectionA, using l-methylamino-Z- chloroindane instead of1-ethylaminovZ-chlorindane, the reaction mixture being stirred at 120Cduring 1 hour. The product recrystallized from ether melts at 120-122C.Yield: 50%.

Analysis: C H N "/1 calculated: 7( found:

B. Preparation of 1-methylamino-2-[N-pheny1-N-('y-diethylaminopropy1)]-aminoindane.

This compound is prepared in the manner described in example 27, sectionC, using 1-methylamino-2- phenylaminoindane instead of 1 -methoxy-2-phenylaminoindane.

EXAMPLE 39.

Preparation of 1-diethy1amino-2- N -phenyl-N-( 'y-diethylaminopropyljaminoindane (formula I R =R C- H,-,; n=2; Z=H B=diethylamino;A=phenyl).

A. Preparation of l-diethylamino-2-phenylaminoindane.

24.5 g (0.094 mol) of l-diethylamino-2-chloroindane and 100 ml ofaniline are stirred during 1 hour at room temperature. After addition of100 ml of chloroform, the aniline hydrochloride is separated byfiltration and the filtrate is evaporated to dryness. The residue isextracted with 200 ml of water, made alkaline and extracted with ether.After drying on potassium carbonate and filtration, the solvents areremoved and the product is distilled. The fraction distilling at165C/0.4 mm is collected. 20.6 g (Yield: ofa product melting at 37-39Cafter recrystallization from petroleum ether (4060C) are obtained.

B. Preparation of 1-diethylamino-2-[N-phenyl-N-( 'ydiethylaminopropyl]-aminoindane.

12.6 g of 1-diethylamino-2-phenylaminoindane are dissolved in 150 ml oftoluene, in the presence of 3.51 g of NaNH- (0.09 mol). After refluxingduring 20 minutes 0.076 mol of y-chloropropyldiethylamine are added, themixture being then further refluxed during 1 hour. After cooling andaddition of m1 of water, the mixture is decanted and extracted by meansof 100 m1 of toluene. The toluene phase is extracted by means of 1 Nhydrochloric acid. The acid extract is made alkaline and extracted withbenzene. After drying of the benzene phase on potassium carbonate, thebenzene is evaporated and the product distilled, The fraction distillingat 210C/0.9 mm is collected 14.8 g (Yield: 83%) of the desired productare obtained.

EXAMPLE 40. Anfllysifil C H N Pfeparatign of "/2 calculated: 69.50 7.3-16.01) "/1 found: 6970 7.22 5.93

1-diethylamino-2-[N-phenyl-N-( ,B-dimethylaminoethyl l-aminoindane(formula I R,=R =CH n=l; Z=H B=diethylamino; A phenyl) This compound isprepared by the method described EXAMPLE 43 in example 39, section B,except that B-chloroethyll dimethylamine is used instead of'y-chloropropyldiethylamine. Yield: 80%. The dihydrochloride obtainedLemmy-2*N-phenyl-N'dlethylam'methyll'immom' Preparation of afterrecrystallization from acetone and methanol melts dime at (formula I R=R =C H 11 1; Z=H. B=OC H l5 A=phenyl) Analysis: C H N Cl A. Preparationof a Calculated: 65.08 8,3 9 g9 16,71-ethoxy-2-(N-phenyl-N-chloracetyl)aminoindane. m U 2.53 g ofl-ethoxy-2-phenylaminoindane. 2.5 ml of 30 the chloride of chloraceticacid and ml of benzene are refluxed during minutes. The mixture isevapo- EXAMPLE rated to dryness and the residue is extracted withpetropreparation of leum ether. Yield: 91%. The desired product melts atl-meth0xy-2-[N-phenyl-N-(diethylaminoethyl)1- 7 7i l42l43C afterrecrystallization from benzene and aminoindane cyclohexane.

r a I: Ri=Re=C2Hs; n= 1; Z=H2; B=OCH =p y 9.6 g ofl-methoxy-2-phenylaminoindane, 2.4 g of Analysis C H N Cl NaNH and 100ml of benzene are refluxed during 30 30 f 6919 435 minutes. 7 g ofB-chloroethyldiethylamine are then found' 69'19 added. The mixture isrefluxed during 48 hours. After cooling, 100 ml of water are added tothe reaction mixture which is then acidified. The aqueous phase is sepa-B- preparation f rated, made alkaline and extracted with chloroform. 2 11\1 h l i h l 1- The chloroform phase is dried and the solvent isreaminoindane moved therefrom, the mixture being then distilled. Thefraction distilling at l74177C/O.1 mm is collected Thls Compound P p asdescnbed example 10.3 g). The hydrochloride of the desired product is30, Section B a usirgg y- 'P l/ prepared in aqueous solution at a pH of5.3. The aque- 40 l y m m n Instead Of yous solution is evaporated anddried with benzene (azep y y n n otropic distillation). 9.7 g of thedesired hydrochloride are obtained. After recrystallization fromethylacetate, EXAMPLE this hydrochloride melts at l45l47C. Preparationof 45 1-ethoxy-2-[N-phenyl N-(diethylaminopropyl)]- aminoindaneAnalvsis: C H N C] (formula I R =R =C H n=2; Z=H B=OC H 7! calculated:70.46 8.33 7.47 9.46 7, found: 70.38 8.33 7.63 9.28 =p y A. Preparationof l-ethoxy-Z- N-phenyl-N-( B-chloropropionyl EXAMPLE 42. aminoindane.Preparation of 2.53 g of l-ethoxy-2-phenylaminoindane, 2.5 ml ofl-methoxy-2-[N-phenyl-N-(B-N'-p P r n0 I yl)lthe chloride of,B-chloropropionic acid and 15 ml of aminoindane. benzene are refluxedduring 30 minutes. The mixture is (formula I I then evaporated todryness and the residue is extracted with petroleum ether (4060C). 2.84g (yield: 85%) R! of the desired product are obtained. Afterrecrystalliza- N =piperidino: tion from petroleum ether (40-60C), thisproduct melts at 92-93c.

11 1; Z=H. B=OCH A=phenyl).

This compound is prepared in the manner described in example 41, exceptthat B-chloroethylpiperidine is Anuhlsiqv C H N Cl used instead ofB-chloroethyldiethylamine. Yield: 50%

The fumarate of the desired product melts at cfllculuwdi 69.86 6.45 4.0710.31

' /z found: (19.89 (1.0] 3.9 l().2

l40-142C after recrystallization from ethylacetate.

B. Parparation of l-ethoxy-2-[N-phenyl-N-(diethylaminopropyl)J-aminoindane.

Analysis: C 5

7: calculated: .4 found:

EXAM PLE 45.

Preparation of l-methoxy-2-[N-phenyl-N-( piperidinopropyl aminoindanehydrochloride.

(formula I A=phenyl;

A. Preparation of l-methoxy-2-(N-phenyl-N-piperidinopropionyl)-aminoindane hydrochloride.

10 g of l-methoxy-2-[N-phenyl-N-(B-chloropropionyl)]-aminoindaneprepared as described in example 31, section A, are dissolved in asolution of piperidine in ethanol. The reaction mixture is refluxedduring 24 hours. After removal of the alcohol, the residue is treatedwith diluted hydrochloric acid. The obtained solution is made alkalineand extracted by means of chloroform. The residue of the chloroformextraction is dissolved in diluted hydrochloric acid and carefully driedunder vacuum. The residue is treated with acetone and the obtainedsolution is filtered. By recrystallization from a mixture of acetone andmethanol the desired hydrochloride is obtained.

B. Preparation of l-methoxy-2-[N-phenyl-N-piperidinopropyl aminoindanehydrochloride.

To a solution of 1-methoxy-2-(N-phenyl-N-piperidinopropionyl)-aminoindane in ether, a suspension of 2 g oflithium aluminum hydride in 100 ml of ether is continuously added. Theobtained mixture is refluxed during 2 hours. After cooling with icewater, ice and water are added to the mixture which is then decanted anddried.

The obtained oil is treated with diluted hydrochloric acid and the pH isthen brought to 6. After extraction with chloroform, the organic phaseis dried and distilled under vacuum. The residue is treated with 100 mlof acetone and heated until a precipitate is obtained. 65

By recrystallization from a mixture of methanol and acetone the desiredproduct melting at 173-l74C is obtained.

Analysis: C H N (I "/1 calculated: 7|.88 8.29 6.98 8.84

'2 found: 72.l)-l 8.20 7.0] 8.64

EXAMPLE 46.

Preparation of l-methoxy-2-lN-phenyl-N-(methylpiperazinopropyl)1-aminoindane trihydrochloride (formula I A=phenyl;

\ r methylpiperazino;

This compound is prepared as described in example 45 usingmethylpiperazine instead of piperidine. The obtained product melts at230-232C.

Analysis: C H N Cl 7: calculated: 58.95 7.42 8.59 2l.75

/r found: 58.92 7.50 8.98 21.40

EXAMPLE 47.

Preparation of l-ethoxy-2-[N-phenyl-N-( diethylaminoethyl aminoindanehydrochloride A. Preparation of 1-ethoxy-2-(N-phenyl-N-diethylaminoacetyl )aminoindane.

This compound is prepared by reacting l-ethoxy-2-(N-phenyl-N-chloroacetyl)-aminoindane (prepared as described in example43, section A) with dimethylamine as described in example 30, section B.

B. Preparation of 1-ethoxy-2- N-phenyl-N-( diethylaminoethyl)aminoindane hydrochloride.

Analysis: C H N Cl 7: calculated: 71.02 8.55 7.20 9.12

71 found: 70.99 8.3l 7.27 9.2]

EXAMPLE 48.

Preparation of l-ethoxy-2-[ N-phen yl-N-( pyrrolidinopropyl aminoindanehydrochloride (formula I A=phenyl;

. \R2 pyrrolidino:

Analysis: C H N Cl "/1 calculated: 71.46 8.28 6.86 9.42

7( found: 71.88 8.2) 6.99 9.46

EXAMPLE 49.

Preparation of l-diethylamino-2-(N-phenyl-N-'y-dimethylaminopropyl)-aminoindane dihydrochloride Analysis:c H N c1 7! calculated: 64.90 8.22 9.80 16.50

/1 found: 65.08 8.31 9.89 16.70

EXAMPLE 50.

Preparation of N-phenyl-N-(y-ethylaminopropyl)-2-aminoindane as well asmono and dichlorhydrochloride thereof.

A. Preparation of N-(B-chloropropionyl)-N-phenyl-2-aminoindane 0.04 molof N-phenyl-Z-aminoindane are acylated by means of 0.06 mol of,8-ch1oropropionyl chloride in 50 cc of benzene. After 5 hours ofreflux, the conversion is complete. The reaction medium is evaporated todryness and the residue is recrystallized from petroleum ether. M.P.85C.

Analysis: C H Cl 7: calculated: 72.11 6.05 1 1.8 7: found: 72.39 6.0111.82

I B. Preparation of N-(B-ethylaminopropionyl)-N-phenyI-Z-aminoindane17.8 g of N-(B-chloropropionyl)-N-phenyl-2- aminoindane and cc of anethanol solution containing 12% by weight of ethylamine are heated at78C during 21 hours in an autoclave. After evaporation of the solvent,the residue is extracted by means of 6 N hydrochloric acid. Aprecipitate of the hydrochloride is obtained by cooling in arefrigerator. By recrystallization from acetone, 19.34 g (yield 188%) ofthe hydrochloride melting at C are obtained.

Analysis: C H C l N 7( calculated: 69.65 7.3 10.28 8.12 7! found: 69677.1 10.4 8.21

The free base is obtained by alkalinization and extraction by means ofether. The residue of the ether phase is used directly in the followingstep.

I C. Preparation of N-phenyl-N-(y-ethylaminopropyl)-2-aminoindane andthe dihydrochloride thereof.

18.9 g of N-(B-ethylaminopropionyl)-N-phenyl-2- aminoindane (0.063 mol)are dissolved in 200 cc of anhydrous ether. The obtained solution isthen poured drop by drop on 0.126 mol (4.8 g) oflithium aluminum hydridesuspended in 100 cc of anhydrous ether. The obtained reaction medium isthen refluxed during 2 hours. After cooling at 0C, 50 cc of water areadded drop by drop. The ether phases are brought together and dried.After evaporation of the ether, 15 g (yield 77%) of a colourless oil areobtained. This product is the free base.

This free base is converted into the dihydrochloride by the usualmethod, using an aqueous acid medium. The aqueous phase is evaporated todryness and the residue is extracted by means of 1N hydrochloric acid.The acid aqueous solution is then evaporated and the residue isrecrystallized from a mixture of methanol and acetone. M.P.: 239-240C.

Analysis of the dihydrochloride: C H N Cl 72 calculated: 65.39 7.68 7.6119.3 7: found: 6521 7.71 7.63 19.18

D Preparation of the monohydrochloride of N-phenyl-N( y-ethylaminopropyl)-2-aminoindane.

1.A NEW DERIVATIVE OF 2-AMINOINDANE OF THE FORMULA:
 2. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1,2 or 3, Z represents two hydrogen atoms or one oxygen atom, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, R2 represents a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro groups in the ortho, meta and/or para position and B represEnts hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
 3. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1,2 or 3, Z represents two hydrogen atoms, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, R2 represents a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro group in the ortho, meta and/or para position and B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
 4. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents two hydrogen atoms, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, R2 represents a lower alkyl group containing 1 to 3 carbon atoms, A represents an unsubstituted phenyl group or a phenyl group substituted by at least one substituent selected among the lower alkyl, lower alkoxy, trifluoromethyl, halo and nitro group in the ortho, meta and/or para position and B represents hydrogen, as well as the pharmaceutically acceptable acid addition salts of said new derivative.
 5. N-phenyl-N-( gamma -ethylaminopropyl)-2-aminoindane as well as the pharmaceutically acceptable acid addition salts thereof.
 6. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents two hydrogen atoms, the (CH2)n group having a straight or branched chain, R1 and R2 which may be identical or different represent each a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, whereby R1 and R2 may also form together with the adjacent nitrogen atom a nitrogenous heterocyclic ring selected among the piperidino, pyrrolidino, morpholino and piperazino rings, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro group in the ortho, meta and/or para position, and B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
 7. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents two hydrogen aToms, the (CH2)n group having a straight or branched chain, R1 and R2 which may be identical or different represent each a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, whereby R1 and R2 may also form together with the adjacent nitrogen atom a nitrogenous heterocyclic ring selected among the piperidino, pyrrolidino, morpholino and piperazino rings, A represents an unsubstituted phenyl radical or a phenyl radical substituted in the ortho, meta and/or para position by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro groups and B represents hydrogen, as well as the pharmaceutically acceptable acid addition salts of said derivative.
 8. N-phenyl-N-diethylaminopropyl-2-aminoindane as well as the pharmaceutically acceptable acid addition salts thereof.
 9. N-phenyl-N-piperidinoethyl-2-aminoindane as well as the pharmaceutically acceptable acid addition salts thereof.
 10. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents an oxygen atom, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, R2 represents a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, whereby R1 and R2 may be identical or different and may form together with the adjacent nitrogen atom a nitrogenous heterocyclic ring selected among the piperidino, pyrrolidino, morpholino and piperazino rings, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro groups in the ortho, meta and/or para position, and B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
 11. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents an oxygen atom, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, R2 represents a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 or 3 carbon atoms, whereby R1 and R2 may be identical or different and may form together with the adjacent nitrogen atom a nitrogenous heterocyclic ring selected among the piperidino, pyrrolidono, morpholino and piperazino ring, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro groups in the ortho, meta and/or para position and B represents hydrogen, as well as the pharmaceutically acceptable acid addition salts of said derivative.
 12. A new derivative of 2-aminoindane according to claim 1, wherein in the Formula (I), n is equal to 1, 2 or 3, Z represents two hydrogen atoms, the (CH2)n group having a straight or branched chain, R1 represents hydrogen, a lower alkyl or hydroxyalkyl or alkynyl radical containing 2 or 3 carbon atoms, R2 represents a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms or a lower alkenyl or alkynyl radical containing 2 to 3 carbon atoms, whereby R1 and R2 may be identical or different and may form together with the adjacent nitrogen atom a nitrogenous heterocyclic ring selected among the piperidino, pyrrolidino, morpholino and piperazino ring, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituent by at least one substituent selected among the lower alkyl, lower alkoxy, hydroxy, trifluoromethyl, halo and nitro groups in the ortho, meta and/or para position and B represents an alkoxy radical containing 1 to 3 carbon atoms, as well as the pharmaceutically acceptable acid addition salts of said derivative. 